Hepatitis delta virus (HDV) is a defective RNA virus that requires HBsAg for replication and transmission. It can cause acute or chronic hepatitis. Chronic infection with HDV is one of the most severe and difficult to treat forms of viral hepatitis. It has been estimated that there is a total of 15-20 million HDV carriers in the world. This review focuses on two fundamental aspects of HDV infection. On the one hand, epidemiological data are summarized, which are essential to understand the real burden of this disease. After the HBV vaccination programs in many countries all over the world, HDV infection has decreased since 1980’s but this decline has not continued further in the last decade. Therefore, HDV infection is still an important public health problem in the world. On the other hand, therapeutic options are described. Currently, interferons are the only option for the treatment of chronic hepatitis delta infection, and pegylated-interferons have shown better results than conventional interferons (IFNs). Monotherapy of nucleos(t)ide analogs have been found ineffective against the HDV infection, but adefovir and pegylated-IFN combination therapy have had some advantages for reduction of HBsAg levels. Trials with more potent nucleoside analogs and pegylated-IFN could be effective in the treatment of chronic HDV infection. New agents like prenylation inhibitors, that can affect the interactions between the large HDV antigen and HBsAg in the HDV virion, will be a hope in treatment of HDV infection.